One in vitro model of the inflammatory immune response is the murine primary antibody response system. We have shown, during the past year, that the response in this system is dependent on the concentration of reduced glutathione in the serum used, and that the enhancement of this response by the addition of 2-mercaptoethanol (2-ME) is a result of its reaction with glutathione. One of the functions of glutathione in vivo is the neutralization of free radicals; therefore we investigated the role of free radicals in this in vitro model of inflammation. Oxygen-derived chemical free radicals (viz., superoxide, hydroxyl, and singlet oxygen) are produced in primary cell cultures, both by active generation by the cells, and by autoxidation of dead cells. These radicals are particularly damaging to cells in the culture. We have found that free radical scavengers such as 2-ME/glutathione and superoxide dismutase can enhance the response of the system to the same degree, independently, and are additive in their effects. The common enhancement of this system by various free radical scavengers provides an in vitro model for the damage to neighboring cells, caused by the generation of free radicals by immunocompetent cells in chronic inflammation.